Stratification Age (<40 vs vs >50) Current (last dose <6 mths) combined oral contraceptive use (Yes vs No) BRCA status (BRCA1 vs BRCA2)

Transcription

1 STICs and STONES: OV.24 A randomized phase II double-blind placebo-controlled trial of Acetylsalicylic acid (ASA) in chemoprevention of ovarian cancer in women with BRCA1/2 mutations/group name and number Co Chairs: Oza A Lheureux S Pathology Chair: Patricia Shaw Senior Investigator: Wendy Parulekar Statistician: Dongsheng Tu Study coordinator: WenLing Liu Sponsor: CCTG Grant Support: CCSRI: Hecht Foundation: CCTG: PM Cancer Foundation: Drug Supply: Apotex GCIG Groups: ANZGOG: K. Phillips ISGO: J. Korach, D. Tsoref NCRI: R. Manchanda Stratification Age (<40 vs vs >50) Current (last dose <6 mths) combined oral contraceptive use (Yes vs No) BRCA status (BRCA1 vs BRCA2)

2 OV.24 / CCTG Trial setting: Women with germline BRCA1/2 mutations scheduled to undergo risk reducing surgery within 6 months to 2 years Study Design: Randomized 2:1, double-blind, placebo controlled phase II Sponsor(s): CCTG, ANZGOG Planned No. of patients: 414 Current accrual: Commencing Fall 2017 in Canada and Australia Other important information: Study has been submitted to Health Canada as pre-clinical Trials Application. Pending further communication with regulatory authorities

3 A phase II, open-label, randomized, multi-centre study of neoadjuvant olaparib in ovarian cancer (NEO Trial) CT CT # CT CT every 9 weeks Biopsy* Biopsy* On progression 6 cycles platinum-based Platinum sensitive HGSOC Olaparib Surgery R chemotherapy Olaparib Maintenance Olaparib ctdna weekly ctdna pre each cycle PIs: Oza AM & Brenton J. Sponsor: PMHC Grant Support: Investigator-initiated, AstraZeneca Global *At each biopsy timepoint- ascitic fluid collection where applicable # Patients to have response or stable disease to proceed to surgery GCIG Groups: Belgium, Italy, New Zealand, and United Kingdom

4 NEO / PMHC Trial setting: Platinum Sensitive Recurrent High Grade Serous Ovarian/Primary Peritoneal or Fallopian tube Cancer Study Design: Phase II, randomized, open-label Sponsor(s): PMHC Planned No. of patients: 75 Current accrual: 5 enrolled, 1 in screening Other important information: If positive signal, study will expand to N=150. Correlatives include: ctdna; BRCA1/2 and HRD analysis; PARP expression; serial biopsy sites to examine heterogeneity of disease; at each biopsy time point ascitic fluid collection (where applicable).

5 A proof of concept, multi-centre, clinical trial of the combination cediranib-olaparib at the time of disease progression on PARP inhibitor in ovarian cancer evolve/pmhc Previous therapy PARP inhibitor >6 months Progression on PARP Cediranib/Olaparib Orally daily Proof of concept study If signal detected, trial continue to randomized phase 2 setting PIs: Oza AM Sponsor: PMHC Grant Support: Investigator-initiated, AstraZeneca Global

6 evolve/pmhc A total of 30 patients with ovarian cancer who progressed on any PARP inhibitor that meet one of the following criteria: Cohort of 10 platinum sensitive with no evidence of disease progression within 6 months of the last dose of platinum based chemotherapy and received PARP as their last line of treatment Cohort of 10 platinum resistant with disease progression within 6 months of the last dose of a platinum based chemotherapy and received PARP inhibitor as their last line of treatment Exploratory cohort of 10 patients who had progressed on PARP and then received standard chemotherapy with further disease progression

7 evolve/pmhc Trial setting: Recurrent high grade serous ovarian cancer Study Design: A multi centre, open-label, proof of concept study investigating the combination cediranib-olaparib at the time of disease progression on PARP inhibitor in ovarian cancer. Sponsor(s): PMHC Planned No. of patients: 31 Current accrual: 16 Other important information: Any prior PARP treatment allowed; platinum sensitive, resistant and exploratory cohorts; ctdna analysis; archival tissue and up to 3 fresh core biopsies at the time of entry, and time of progression; germline BRCA1/2; PG analysis.

8 SUPPLEMENTAL SLIDES

9 OV.24 / CCTG Stratification Age (<40 vs vs >50) Current (last dose <6 mths) combined oral contraceptive use (Yes vs No) BRCA status (BRCA1 vs BRCA2)

10 OV.24 / CCTG Secondary To assess Patient Acceptance of Intervention of Chemoprevention Studies in this High-risk Female Cohort Tertiary To characterize the Effect of Aspirin on HGSOC Tumourigenesis Link between Tumourigenesis and Microenvironment Hormone stimulation Inflammatory cell phenotype Markers of inflammation and oncogenic pathway expression Biobanking for future correlative studies